Metabolic Vulnerability Index predicts mortality in older adults based on markers of inflammation and dysmetabolism
4 affiliations
- 1Diagnostics Research and Development, Labcorp, Morrisville, North Carolina, United States of America
- 2Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, United States of America
- 3Department of Medicine, Duke University School of Medicine, Durham, North Carolina, United States of America
- 4Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Abstract
Traditional clinical metrics fail to capture the complex interplay among metabolic health, inflammation, and nutritional status contributing to aging-related morbidity and mortality. The Metabolic Vulnerability Index (MVX) integrates measures of inflammation and metabolic health to assess mortality risk. Using clinical nuclear magnetic resonance spectra and a validated MVX algorithm, MVX scores were generated for the Duke Established Populations for Epidemiologic Studies of the Elderly (D-EPESE) longitudinal cohort (n = 1507, mean age 78.1 ± 5.4 years; 36% men). MVX comprises markers of chronic inflammation (small high density lipoproteins and the inflammation marker, GlycA) and metabolic malnutrition (citrate and branched chain amino acids). Incident all-cause deaths were ascertained over a median follow-up of 7.0 years (95% confidence interval (CI):1.0–18.9). In models adjusted for age, sex, and race, greater MVX scores were strongly associated with 1-year mortality [hazard ratio (HR) per 1 standard (SD): 3.00 (CI: 2.34–3.85, p < 0.0001)]. After further adjustment for body mass index, type 2 diabetes, smoking, systolic blood pressure, total cholesterol, triglycerides, eGFR, and qualitative measures of health and physical function, the association persisted, with only modest attenuation [HR: 2.35 (CI: 1.76–3.14, p < 0.0001)]. Similar associations were observed for 2-, 5- and 10-year mortality, with some attenuation over longer follow-up. Participants in the greatest MVX quartile had significantly greater mortality risk (Kaplan-Meier, p < 0.0001). The 1-year AUROC for mortality was 0.77 (CI: 0.71–0.84), outperforming questionnaire-based measures of health and physical function, as well as the individual MVX components (p < 0.0001). Our findings suggest that MVX is a prognostic, biomarker-derived test that integrates markers of inflammation, metabolic dysfunction, and malnutrition to predict short- and long-term mortality in adults >70 years. MVX may provide additional clinical information to support personalized risk stratification and guide targeted approaches for older adults. Author summary: The recently developed Metabolic Vulnerability Index (MVX) is a prognostic, blood-based test that combines biomarkers of chronic inflammation, metabolic dysfunction and malnutrition into a single score predicting risk of death, even in people who appear healthy. The goal of this study was to see if the MVX test performs well in adults aged >70 years, a group for whom early identification of declining health is especially valuable. Using a large, well-characterized cohort of older adults, we determined that the MVX test identified patients at risk of dying within 1–10 years, even after accounting for many clinical risk factors: age, sex, race, body mass index, type 2 diabetes, smoking, systolic blood pressure, lipids, kidney function, and qualitative measures of health and physical function. MVX also outperformed commonly used questionnaire-based health assessments at predicting short-term mortality risk. Because the test includes biomarkers of malnutrition, dysmetabolism and inflammation, we believe it will be useful to healthcare providers by identifying older adults who could use additional diagnostic tools to differentiate patients who are healthy from those who may have underlying disease. Most importantly, every biomarker underlying the MVX score is modifiable through diet, exercise or medical treatment. Thus, a high score does not just flag risk but points toward specific steps a provider and patient can take together to lower that risk.
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BibTeX
@article{connelly2026metabolic,
title = {{Metabolic Vulnerability Index predicts mortality in older adults based on markers of inflammation and dysmetabolism}},
author = {Margery A. Connelly and Irina Shalaurova and Leanna M. Ross and Robin P. F. Dullaart and William E. Kraus and Virginia Byers Kraus},
journal = {PLOS Aging and Health},
year = {2026},
month = oct,
doi = {10.1371/journal.page.0000018},
url = {https://doi.org/10.1371/journal.page.0000018},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Metabolic Vulnerability Index predicts mortality in older adults based on markers of inflammation and dysmetabolism
AU - Margery A. Connelly
AU - Irina Shalaurova
AU - Leanna M. Ross
AU - Robin P. F. Dullaart
AU - William E. Kraus
AU - Virginia Byers Kraus
PY - 2026
DA - 2026/10/09
JO - PLOS Aging and Health
DO - 10.1371/journal.page.0000018
UR - https://doi.org/10.1371/journal.page.0000018
AB - Traditional clinical metrics fail to capture the complex interplay among metabolic health, inflammation, and nutritional status contributing to aging-related morbidity and mortality. The Metabolic Vulnerability Index (MVX) integrates measures of inflammation and metabolic health to assess mortality risk. Using clinical nuclear magnetic resonance spectra and a validated MVX algorithm, MVX scores were generated for the Duke Established Populations for Epidemiologic Studies of the Elderly (D-EPESE) longitudinal cohort (n = 1507, mean age 78.1 ± 5.4 years; 36% men). MVX comprises markers of chronic inflammation (small high density lipoproteins and the inflammation marker, GlycA) and metabolic malnutrition (citrate and branched chain amino acids). Incident all-cause deaths were ascertained over a median follow-up of 7.0 years (95% confidence interval (CI):1.0–18.9). In models adjusted for age, sex, and race, greater MVX scores were strongly associated with 1-year mortality [hazard ratio (HR) per 1 standard (SD): 3.00 (CI: 2.34–3.85, p < 0.0001)]. After further adjustment for body mass index, type 2 diabetes, smoking, systolic blood pressure, total cholesterol, triglycerides, eGFR, and qualitative measures of health and physical function, the association persisted, with only modest attenuation [HR: 2.35 (CI: 1.76–3.14, p < 0.0001)]. Similar associations were observed for 2-, 5- and 10-year mortality, with some attenuation over longer follow-up. Participants in the greatest MVX quartile had significantly greater mortality risk (Kaplan-Meier, p < 0.0001). The 1-year AUROC for mortality was 0.77 (CI: 0.71–0.84), outperforming questionnaire-based measures of health and physical function, as well as the individual MVX components (p < 0.0001). Our findings suggest that MVX is a prognostic, biomarker-derived test that integrates markers of inflammation, metabolic dysfunction, and malnutrition to predict short- and long-term mortality in adults >70 years. MVX may provide additional clinical information to support personalized risk stratification and guide targeted approaches for older adults. Author summary: The recently developed Metabolic Vulnerability Index (MVX) is a prognostic, blood-based test that combines biomarkers of chronic inflammation, metabolic dysfunction and malnutrition into a single score predicting risk of death, even in people who appear healthy. The goal of this study was to see if the MVX test performs well in adults aged >70 years, a group for whom early identification of declining health is especially valuable. Using a large, well-characterized cohort of older adults, we determined that the MVX test identified patients at risk of dying within 1–10 years, even after accounting for many clinical risk factors: age, sex, race, body mass index, type 2 diabetes, smoking, systolic blood pressure, lipids, kidney function, and qualitative measures of health and physical function. MVX also outperformed commonly used questionnaire-based health assessments at predicting short-term mortality risk. Because the test includes biomarkers of malnutrition, dysmetabolism and inflammation, we believe it will be useful to healthcare providers by identifying older adults who could use additional diagnostic tools to differentiate patients who are healthy from those who may have underlying disease. Most importantly, every biomarker underlying the MVX score is modifiable through diet, exercise or medical treatment. Thus, a high score does not just flag risk but points toward specific steps a provider and patient can take together to lower that risk.
SN - 3070-801X
ER -